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Genetics and vaccine response

Vaccines used in livestock production have come a long way, and reach the market only after extensive testing to demonstrate their efficacy. But while modern vaccines offer clear benefits in reducing cattle disease, producers and veterinarians know that sometimes even vaccinated cattle get sick. Reasons for variable vaccine response can include differences in exposure levels, nutrition or other environmental factors, and as South Dakota State University animal scientist Michael Gonda, PhD., explained at last-week’s BIF conference, so can genetics.

Gonda outlined his team’s research into the genetic component of vaccine response, and the potential for including the trait in genetic evaluation and selection of beef cattle. Several studies, Gonda notes, have explored the genetics of disease resistance in cattle and have identified genetic markers related to resistance. In most of these studies though, non-infected animals are assumed to be resistant to the disease, he notes, while other factors such as non-exposure or false-negative testing could compound the results.

An alternative phenotype for disease resistance, he says, is measurement of immune response to commercially available vaccines. His hypothesis was that vaccine response in cattle is a heritable trait and researchers could identify DNA markers associated with vaccine response. These DNA markers could then be used to develop a DNA test for vaccine response. His study focused on response to a Bovine Viral Diarrhea Virus (BVDV) vaccine.

In one of the experiments, researchers sampled 267 Angus and Angus-influenced calves from three herds in different South Dakota locations. The calves were vaccinated with Pyramid-5, which includes BVDV-1 and BVDV-2, at 1 to 8 months of age. Gonda notes the calves had not previously been vaccinated for BVDV, although dams had been vaccinated. The researchers collected blood samples from the calves at the time of vaccination and 21 to 28 days post-vaccination. They used the blood sample at time of vaccination for DNA isolation, measurement of baseline BVDV antibodies and for identification of calves persistently infected (PI) with BVDV. If a PI calf was identified, he says, all of the calves in the same contemporary group would likely have been exposed to BVDV prior to vaccination would need to be removed from the study. Fortunately they did not find any PI calves.

The post-vaccination blood sample was used to measure BVDV-specific antibodies circulating in blood post-vaccination, using a .BVDV-specific ELISA test. The team calculated vaccine response by subtracting BVDV antibodies present at time of vaccination from BVDV antibodies present post-vaccination. They also identified the sire of each calf, using DNA parentage testing at one site and herd records at the others.

The team found that the sire of the calf was significantly associated with vaccine response in this study. Gonda notes that as prior studies have shown vaccine response is heritable for other vaccines in cattle and in humans, his results suggest that BVDV vaccine response is heritable in cattle. Because of the small number of calves in the study, the researchers did not estimate a heritability level for BVDV vaccine response.

It should be possible, he adds, to identify DNA markers associated with BVDV vaccine response which can be used for genetic selection.

Development of a DNA test for vaccine response will, however, be a long process he warns, noting that several questions remain to be answered. These include:

What is the genetic correlation between vaccine response and disease susceptibility?

How should vaccine response be measured? Should we focus on measures of the humoral (antibody) immune response, the cell-mediated immune response, or both?

What is the genetic correlation between vaccine response and other economically important traits?

Which DNA markers are associated with vaccine response? After discovery, these associations will need to be confirmed in an independent gene mapping population before use.

How can we best transition from discovery of DNA markers associated with animal health to implementation of a tool useful for producers for making selection decisions?